Allograft Dysfunction in Liver Transplant Patients Treated with Pegylated Interf

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Allograft Dysfunction in Liver Transplant Patients Treated with

Pegylated Interferon Plus Ribavirin for Hepatitis C

Liver transplantation is currently the only treatment for chronic

hepatitis C patients who develop decompensated liver cirrhosis or

advanced hepatocellular carcinoma. Unfortunately, hepatitis C virus

(HCV) almost always re-infects the new liver soon after

transplantation.

Post-transplant hepatitis C therapy is undergoing intensive study,

but the side effects of interferon and ribavirin make treatment

difficult or impossible for many patients. Interferon may trigger

autoimmune disorders in individuals with well-functioning immune

systems, and there is concern that it might trigger autoimmune

hepatitis following a transplant.

As described in the February 2007 issue of Gut, Italian researchers

studied 44 liver transplant recipients with hepatitis C who received

pegylated interferon alpha-2b (PegIntron) plus ribavirin for at least

6 months for HCV recurrence. They performed laboratory,

microbiological, imaging, and histological assessments to identify

the origin of allograft (donor liver) dysfunction.

Results

• 9 of 44 transplanted patients developed allograft dysfunction.

• 8 of these did so despite HCV RNA clearance while on pegylated

interferon plus ribavirin.

• Infections (other than HCV), anastomoses (blood vessel)

complications, and organ rejection were excluded as causes of graft

dysfunction.

• In all cases, pre-existing (prior to transplantation) autoimmune

hepatitis was also ruled out.

• All 9 patients had scores suggesting probable autoimmune hepatitis

(+10 to +14).

• 3 individuals developed other autoimmune disorders (cholangitis,

autoimmune thyroiditis, systemic lupus erythematosus).

• Use of anti-lymphocyte antibodies in immunosoppressive induction

therapy was associated with the development of graft dysfunction.

• Use of granulocyte colony-stimulating factor (G-CSF) to treat

interferon-induced neutropenia showed a protective role.

• Withdrawal of anti-HCV therapy and treatment with prednisone did

not produce consistent outcomes.

• 5 patients experienced remission of liver dysfunction, while 4

experienced graft failure (with 2 deaths).

Conclusion

In conclusion, the authors wrote, " De novo autoimmune hepatitis

should be considered in differential diagnosis along with rejection

in liver transplanted patients developing graft dysfunction while on

interferon treatment. "

Reference

S Berardi, F Lodato, A Gramenzi, and others. High incidence of

allograft dysfunction in liver transplant patients treated with Peg-

Interferon alfa-2b and Ribavirin for hepatitis C recurrence: possible

de novo autoimmune hepatitis? Gut 56(2): 237-242. February 2007.